After failure of primary therapy, any one of these independent risk factors can signal a patient at high risk for prostate cancer-specific mortality¹:

• Short time to biochemical recurrence
• Rapid PSA-DT*
• High Gleason score

Together, these risk factors can be a deadly combination.

      *PSA-DT is the time it takes for a PSA value to double after PSA returns to measurable levels following failure of therapy of curative intent²

† Radical prostatectomy                               Adapted from Freedland. JAMA; July 2005¹

• Two retrospective analyses of patients with Stage T1b-T3 prostate cancer who underwent radical prostatectomy at The Johns Hopkins Hospital were reported in 1999 by Pound et al (N=1997) and in 2005 by Freedland et al (N=5096)^3,1
  


• Of 5096 patients, data from 379 patients with biochemical recurrence and information on PSA-DT were used to estimate the risk of prostate cancer-specific mortality as reported in the table above¹
  


• There were wide confidence intervals around some of the estimates, and some groups consisted of a small number of patients. This may limit the value of these data for prognostic purposes¹
  


• Patients did not receive adjuvant radiation or hormonal therapy prior to biochemical recurrence¹
  

THESE FACTORS CAN ALSO SIGNAL INCREASED RISK OF METASTATIC DISEASE

After failure of therapy of curative intent—
With short time to biochemical recurrence after radiation therapy (RT):

• Patients with biochemical recurrence < 12 months after RT were 3 times more likely to develop distant metastases by 5 years vs patients who had a biochemical recurrence > 12 months after RT: 75% vs 25%, respectively ( P< 0.001)⁴
  


• These findings are from a retrospective analysis of 494 patients with Stage T1-T3 prostate cancer treated with RT. Of this group, 151 patients were found to have a profile of increasing PSA after treatment, and 45 of these had developed evidence of distant metastases. Based on these data, the actuarial rate of distant metastases development was estimated for all 151 patients
  


• Of the 151 patients, 79 received hormonal therapy—48 at the time of clinical recurrence and 31 before clinically evident recurrent disease⁴
  


• A short median follow-up (26 months from biochemical recurrence) and use of hormonal therapy prior to clinical recurrence may limit the value of these data⁴
  

With rapid PSA doubling time after radical prostatectomy (RP):

• In a retrospective analysis to determine the clinical predictors of positive bone scans and pelvic computerized tomography (CT), 128 patients with T2-T4 prostate cancer and biochemical recurrence after RP (mean time from RP to biochemical failure = 28 months) had pelvic CT and/or bone scans. A total of 97 bone scans and 71 CT scans were performed⁵
  

After RT, clinical recurrence plus PSA-DT < 8 months is predictive of metastatic disease⁶

• In a retrospective analysis to determine PSA parameters in 841 patients with clinically localized or locally advanced prostate cancer, 263 patients were found to have rising PSA profiles after RT⁶
  


• Of these, 145 patients were found to have clinical recurrence (n=118 local, 7 pelvic nodal, 40 distant metastatic) as determined by bone scan, CT, or biopsy. Based on these data, the actuarial rate of distant metastases was estimated⁶

With combined risk factors, metastatic disease can develop within 3 years.⁶

Estimated rates of metastatic disease were striking in patients with a biochemical recurrence within one year after RT and a PSA-DT of < 8 months (n=43).⁶

• At 3 years 50% of patients developed metastatic disease⁶
• At 6.5 years 100% of patients were projected to develop metastases⁶

Identify and closely monitor high-risk patients to help determine onset of metastatic disease.

References:

1. Freedland SJ, Humphreys EB, Mangold LA, et al. Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA. 2005;294:433-439.
   
   
2. Studies shed more light on value of “PSA kinetics” in prostate cancer. National Cancer Institute Cancer Bulletin. 2005;32:3.
   
   
3. Pound CR, Partin AW, Eisenberger MA, et al. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999;281:1591-1597.
   
   
4. Lee WR, Hanks GE, Hanlon A. Increasing prostate-specific antigen profile following definitive radiation therapy for localized prostate cancer: clinical observations. J Clin Oncol. 1997;15:230-238.
   
   
5. Okotie OT, Aronson WJ, Wieder JA, et al. Predictors of metastatic disease in men with biochemical failure following radical prostatectomy. J Urol. 2004;171:2260-2264.
   
   
6. Zagars GK, Pollack A. Kinetics of serum prostate-specific antigen after external beam radiation for clinically localized prostate cancer. Radiother Oncol. 1997;44:213-221.
   
   

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